Bacterial skin infections, especially by Staphylococcus aureus, can both initiate and propagate[unreadable] many inflammatory skin diseases, particularly atopic dermatitis (AD). The mechanisms by which[unreadable] this occurs are unclear, but many lines of evidence implicate the involvement of biologically active[unreadable] staphylococcal bacterial products such as superantigen toxins, alpha toxin, and the cell-wall[unreadable] lipoprotein lipoteichoic acid (LTA). The ability of these staphylococcal products to stimulate[unreadable] cytokine production in keratinocytes could provide one mechanism by which staphylococcal skin[unreadable] infections worsen AD. Both preliminary and published data from our group indicate that the lipid[unreadable] mediator platelet-activating factor (PAF) can modulate the effects of these bacterial products on[unreadable] keratinocyte cytokine production. Three specific aims are planned to help define the mechanism(s)[unreadable] by which bacterial products worsen skin disease which will allow novel treatment strategies for[unreadable] patients with infected atopic dermatitis. The first objective will define the levels of these[unreadable] staphylococcal products on clinically infected AD lesions, and generate biologically active wash fluid[unreadable] from infected AD lesions for further studies for both this Project as well as for Project 2. The[unreadable] second aim will use two novel model systems with PAF-R and toll-receptor-positive and -negative[unreadable] epidermal cells to define the role of the PAF-R versus toll-like receptors in bacterial productmediated[unreadable] cytokine production. The third objective will examine the ability of bacterial products to[unreadable] induce cutaneous inflammation both in wild-type and a novel mouse model of atopic disease[unreadable] (StatGVT mice). PAF-R-/- and MyD88-/- mice will be used to define the role of the PAF and toll-like[unreadable] receptor system in these processes.